S-038 also includes additional proposed modifications to the approved risk evaluation and mitigation strategy (REMS), comprising further revisions to the Medication Guide as well as

To facilitate review of your submission, provide a highlighted or marked- up copy that shows all changes, as well as a clean Microsoft Word version.

In addition, the proposed modification includes revisions to the Chantix REMS goal to focus only on neuropsychiatric risks.

Alternatively, updates may be made by modifying the complete previous REMS supporting document, with all changes marked and highlighted.

should include prominent disclosure of the important new safety information that appears in the revised package labeling.

The meta-analysis showed higher rates of CV endpoints in patients on CHANTIX relative to placebo across different time frames and pre-specified sensitivity analyses, including various study groupings and CV outcomes.

The following inactive ingredients are included in the tablets: microcrystalline cellulose, anhydrous dibasic calcium phosphate, Reference ID: 3630834 croscarmellose sodium, colloidal silicon dioxide, magnesium stearate, Opadry® White (for 0.5 mg), Opadry® Blue (for 1 mg), and Opadry® Clear.

V arenicline blocks the ability of nicotine to activate 114(32 receptors and thus to stimulate the central nervous me.solimbic dopamine system, believed to be the neuronal mechanism underlying reinforcement and reward experienced upon smoking.

There was no evidence of a carcinogenic effect in mice administered varenicline by oral gavage for 2 years at doses up to 20 mg/kg/day (47 times the maximum recommended human daily exposure based on AUC).

Some people have had serious side effects while using CHANTIX to help them quit smoking, including: New or worse mental health problems, such as changes in behavior, hostility, agitation, depressed mood, and suicidal thoughts or actions.

17.13 Driving or Operating Machinery 17.14 Vivid, Unusual, or Strange Dreams Medication Guide 17.15 Pregnancy and Lactation 17.1 Initiate Treatment and Continue to Attempt to Quit if Lapse 17.2 How To Take *Sections or subsections omitted from the full prescribing information are not 17.3 Starting Week Dosage listed.

The meta-analysis showed higher rates of CV endpoints in patients on CHANTIX relative to placebo across different time frames and pre-specified sensitivity analyses, including various study groupings and CV outcomes.

The following inactive ingredients are included in the tablets: microcrystalline cellulose, anhydrous dibasic calcium phosphate, croscarmellose sodium, colloidal silicon dioxide, magnesium stearate, Opadry® White (for 0.5 mg), Opadry® Blue (for 1 mg), and Opadry® Clear.

Varenicline blocks the ability of nicotine to activate α4β2 receptors and thus to stimulate the central nervous mesolimbic dopamine system, believed to be the neuronal mechanism underlying reinforcement and reward experienced upon smoking.

There was no evidence of a carcinogenic effect in mice administered varenicline by oral gavage for 2 years at doses up to 20 mg/kg/day (47 times the maximum recommended human daily exposure based on AUC).

17.9 Nicotine Withdrawal 17.10 Angioedema 17.11 Serious Skin Reactions 17.12 Patients with Cardiovascular Disease 17.13 Driving or Operating Machinery 17.14 Vivid, Unusual, or Strange Dreams 17.15 Pregnancy and Lactation *Sections or subsections omitted from the full prescribing information are not listed.

In a human laboratory abuse liability study, a single oral dose of 1 mg varenicline did not produce any significant positive or negative subjective responses in smokers.

Varenicline blocks the ability of nicotine to activate α4β2 receptors and thus to stimulate the central nervous mesolimbic dopamine system, believed to be the neuronal mechanism underlying reinforcement and reward experienced upon smoking.

There was no evidence of a carcinogenic effect in mice administered varenicline by oral gavage for 2 years at doses up to 20 mg/kg/day (47 times the maximum recommended human daily exposure based on AUC).

If you, your family, or caregiver notice agitation, hostility, depression or changes in behavior or thinking that are not typical for you, or you develop any of the following symptoms, stop taking CHANTIX and call your doctor right away: • thoughts about suicide or dying, or attempts to commit suicide • new or worse depression, anxiety, or panic attacks • feeling very agitated or restless • acting aggressive, being angry, or violent • acting on dangerous impulses • an extreme increase in activity and talking (mania)